Pre-administration of turmeric prevents methotrexate-induced liver toxicity and oxidative stress

Abstract

BackgroundMethotrexate (MTX) is an antimetabolite broadly used in treatment of cancer and autoimmune diseases. MTX-induced hepatotoxicity limits its application. We investigated hepatoprotective effects of turmeric in MTX-induced liver toxicity.MethodsAll experiments were performed on male Wistar albino rats that were randomly divided into six groups. Group one received saline orally for 30 days (control group), groups two and three received turmeric extract (100, 200 mg/kg respectively) orally for 30 days, group four received single dose, of MTX IP at day 30, groups five and six received turmeric extract 100 and 200 mg/kg orally respectively for 30 days and single dose of methoterxate IP (20 mg/kg) at day 30. Four days after MTX injection animals were sacrificed and evaluated. Blood ALT and AST (indicators of hepatocyte injury), ALP and bilirubin (markers of biliary function), albumin (reflect liver synthetic function) as well as the plasma TAS concentration (antioxidant defenses) were determined. The cellular antioxidant defense activities were examined in liver tissue samples using SOD, CAT, and GSH-Px for the oxidative stress, and MDA for lipid peroxidation. In addition, liver damage was evaluated histopathologically.ResultsMTX significantly induced liver damage (P < 0.05) and decreased its antioxidant capacity, while turmeric was hepatoprotective. Liver tissue microscopic evaluation showed that MTX treatment induced severe centrilobular and periportal degeneration, hyperemia of portal vein, increased artery inflammatory cells infiltration and necrosis, while all of histopathological changes were attenuated by turmeric (200 mg/kg).ConclusionTurmeric extract can successfully attenuate MTX-hepatotoxicity. The effect is partly mediated through extract’s antinflammatory activity.

Structure and properties of slow-resorbing nanofibers obtained by (co-axial) electrospinning as tissue scaffolds in regenerative medicine

“…On th eother hand, many viruses preferentially, or exclusively replicate in dividing cells; hence their components are potentially becoming an important source/inspiration in the search of drugs that preferentially target cancer stem cells [33][34][35][36]. Beside viral methods, some clinically tested as well as new drugs with preferential toxicity towards cancer stem cells are increasingly becoming available [37][38][39][40][41]. Such tasks are facilitated by recent progress in methodologies that allows for better detection and monitoring of cancer stem cells [25,26,39].…”

Protective Effects of Biochanin A against Methotrexate-Induced Acute Liver Injury in Rats

“…19,20 The deleterious effects of oxidative damage caused by MTX could be attributed to lipid peroxidation. 6,7,8,21 MDA levels, an end product of lipid peroxidation chain and a useful marker for lipid peroxidation, are known to be increased in response to oxidative stress status. 16,22 The result of increased liver MDA levels in the present study suggests the presence of increased lipid peroxidation induced by MTX.…”

“…Free radicals-induced oxidative stress can lead to apoptosis, cell death, and tissue damage. 6,7,8 Therefore, it is believed that administration of antioxidant may inhibit the MTX-induced liver damage. Biochanin A (5, 7-Dihydroxy-4′-methoxyisoflavone, BCA) is a member of a natural organic compound classified under the phytochemicals known as isoflavonoids.…”

Protective effects of tumor necrosis factor alpha inhibitors on methotrexate-induced pancreatic toxicity

“…It has been proposed in recent studies that MTX has a cytotoxic effect in reducing intracellular tetrahydrofolate, but the mechanism of MTX-induced toxicity is not well known. 1,2,[4][5][6][7][8][9][10][11] Methotrexate has been used in the treatment of pancreatic cancer, but there has been no research into its side effects on the pancreas, an organ which is relatively sensitive to various toxic substances and drugs. High-dose substances, causing oxidative stress, have been reported to have a toxic effect on the pancreas.…”

“…High-dose substances, causing oxidative stress, have been reported to have a toxic effect on the pancreas. 1,[5][6][7][8][9][10][11] However, the development of tolerance to MTX has been reported in patients over time. The tolerance mechanism of the metabolites in MTX is not known.…”